Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change

Journal of Structural Biology
Arun Prasad PanduranganMaya Topf

Abstract

Fitting of atomic components into electron cryo-microscopy (cryoEM) density maps is routinely used to understand the structure and function of macromolecular machines. Many fitting methods have been developed, but a standard protocol for successful fitting and assessment of fitted models has yet to be agreed upon among the experts in the field. Here, we created and tested a protocol that highlights important issues related to homology modelling, density map segmentation, rigid and flexible fitting, as well as the assessment of fits. As part of it, we use two different flexible fitting methods (Flex-EM and iMODfit) and demonstrate how combining the analysis of multiple fits and model assessment could result in an improved model. The protocol is applied to the case of the mature and empty capsids of Coxsackievirus A7 (CAV7) by flexibly fitting homology models into the corresponding cryoEM density maps at 8.2 and 6.1Å resolution. As a result, and due to the improved homology models (derived from recently solved crystal structures of a close homolog - EV71 capsid - in mature and empty forms), the final models present an improvement over previously published models. In close agreement with the capsid expansion observed in the EV71 s...Continue Reading

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Citations

Apr 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Tzviya Zeev-Ben-MordehaiKay Grünewald
Mar 22, 2015·Current Opinion in Structural Biology·Giorgio E TamòMatteo Dal Peraro
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Aug 26, 2015·Journal of Applied Crystallography·Irene FarabellaMaya Topf
Jan 7, 2021·Acta Crystallographica. Section D, Structural Biology·Tristan CragnoliniMaya Topf

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Methods Mentioned

BETA
electron cryo-microscopy
X-ray
NMR

Software Mentioned

QMEAN
TEMPy
RIBFIND
VIPERdb
iMODfit
MODELLER
EM
TASSER
Chimera fit _ in _ map
DSSP

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